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Idebenone protects against spontaneous chronic murine colitis by alleviating endoplasmic reticulum stress and inflammatory response


Shastri, S and Shinde, T and Perera, AP and Gueven, N and Eri, R, Idebenone protects against spontaneous chronic murine colitis by alleviating endoplasmic reticulum stress and inflammatory response, Biomedicines, 8, (10) Article 384. ISSN 2227-9059 (2020) [Refereed Article]


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Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.3390/biomedicines8100384


Endoplasmic reticulum (ER) stress in intestinal secretory goblet cells has been linked to the development of ulcerative colitis (UC). Emerging evidence suggests that the short chain quinone drug idebenone displays anti-inflammatory activity in addition to its potent antioxidant and mitochondrial electron donor properties. This study evaluated the impact of idebenone in Winnie mice, that are characterized by spontaneous chronic intestinal inflammation and ER stress caused by a missense mutation in the mucin MUC2 gene. Idebenone (200 mg/kg) was orally administered daily to 56 weeks old Winnie mice over a period of 21 days. Idebenone treatment substantially improved body weight gain, disease activity index (DAI), colon length and histopathology score. Immunohistochemistry revealed increased expression of MUC2 protein in goblet cells, consistent with increased MUC2 mRNA levels. Furthermore, idebenone significantly reduced the expression of the ER stress markers C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and X-box binding protein-1 (XBP-1) at both mRNA and protein levels. Idebenone also effectively reduced pro-inflammatory cytokine levels in colonic explants. Taken together, these results indicate that idebenone could represent a potential therapeutic approach against human UC by its strong anti-inflammatory activity and its ability to reduce markers of ER stress.

Item Details

Item Type:Refereed Article
Keywords:chronic colitis, endoplasmic reticulum stress, idebenone, mucin, pro-inflammatory cytokines, <i>Winnie</i>
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Pharmaceutical sciences
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Shastri, S (Mrs Sonia Shastri)
UTAS Author:Shinde, T (Ms Tanvi Shinde)
UTAS Author:Perera, AP (Mrs Agampodi Perera)
UTAS Author:Gueven, N (Dr Nuri Guven)
UTAS Author:Eri, R (Associate Professor Raj Eri)
ID Code:141342
Year Published:2020
Web of Science® Times Cited:1
Deposited By:Pharmacy
Deposited On:2020-10-15
Last Modified:2020-11-17

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